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Departments of
*
Pathophysiology and Immunology,
Rehabilitation, and
Connective Tissue Disease, Institute of Rheumatology, Warsaw, Poland
Recent data suggest that IL-15 plays an important role in the
pathogenesis of rheumatoid arthritis. In the present study, we
hypothesized that elevated in the joints of rheumatoid arthritis, but
not osteoarthritis, patients, IL-15 may exert its proinflammatory
properties via the induction of IL-17, a cytokine known to stimulate
synoviocytes to release several mediators of inflammation including
IL-6, IL-8, GM-CSF and PGE2. To test this hypothesis, we
first measured the levels of IL-17 and IL-15 using specific ELISA and
found that synovial fluids of patients with rheumatoid arthritis, but
not with osteoarthritis, contain high levels of these cytokines. A
strong correlation between IL-15 and IL-17 levels in synovial fluids
was observed. Among tested factors, LPS and TNF-
failed, IL-15 and
IL-2 were equipotent, and PMA + ionomycin was far more efficient in the
induction of IL-17 secretion by PBMCs isolated from healthy blood
donors. Interestingly, synovial fluid cells, in contrast to PBMCs
isolated from patients with rheumatoid arthritis, but not
osteoarthritis, respond to PMA + ionomycin with much lower, comparable
to IL-15-triggered IL-17 secretion. Moreover, PMA + ionomycin-triggered
IL-17 secretion is completely or partially blocked in the presence of
low doses of cyclosporin A or high doses of methylprednisolone,
respectively. IL-15-triggered IL-17 secretion by PBMCs was completely
inhibited by these drugs. Thus, our results suggest for the first time
that IL-15 may represent a physiological trigger that via cyclosporin A
and steroid sensitive pathways leads to the overproduction of IL-17 in
the joints of rheumatoid arthritis patients.
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X. K. Liu, X. Lin, and S. L. Gaffen Crucial Role for Nuclear Factor of Activated T Cells in T Cell Receptor-mediated Regulation of Human Interleukin-17 J. Biol. Chem., December 10, 2004; 279(50): 52762 - 52771. [Abstract] [Full Text] [PDF]
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S. Ferrari-Lacraz, E. Zanelli, M. Neuberg, E. Donskoy, Y. S. Kim, X. X. Zheng, W. W. Hancock, W. Maslinski, X. C. Li, T. B. Strom, et al. Targeting IL-15 Receptor-Bearing Cells with an Antagonist Mutant IL-15/Fc Protein Prevents Disease Development and Progression in Murine Collagen-Induced Arthritis J. Immunol., November 1, 2004; 173(9): 5818 - 5826. [Abstract] [Full Text] [PDF]
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L. A. Lieberman, F. Cardillo, A. M. Owyang, D. M. Rennick, D. J. Cua, R. A. Kastelein, and C. A. Hunter IL-23 Provides a Limited Mechanism of Resistance to Acute Toxoplasmosis in the Absence of IL-12 J. Immunol., August 1, 2004; 173(3): 1887 - 1893. [Abstract] [Full Text] [PDF]
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M. Umemura, T. Kawabe, K. Shudo, H. Kidoya, M. Fukui, M. Asano, Y. Iwakura, G. Matsuzaki, R. Imamura, and T. Suda Involvement of IL-17 in Fas ligand-induced inflammation Int. Immunol., August 1, 2004; 16(8): 1099 - 1108. [Abstract] [Full Text] [PDF]
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M.-E. Miranda-Carus, A. Balsa, M. Benito-Miguel, C. Perez de Ayala, and E. Martin-Mola IL-15 and the Initiation of Cell Contact-Dependent Synovial Fibroblast-T Lymphocyte Cross-Talk in Rheumatoid Arthritis: Effect of Methotrexate J. Immunol., July 15, 2004; 173(2): 1463 - 1476. [Abstract] [Full Text] [PDF]
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D. O'Gradaigh and J. E. Compston T-cell involvement in osteoclast biology: implications for rheumatoid bone erosion Rheumatology, February 1, 2004; 43(2): 122 - 130. [Full Text] [PDF]
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C. A. Murphy, C. L. Langrish, Y. Chen, W. Blumenschein, T. McClanahan, R. A. Kastelein, J. D. Sedgwick, and D. J. Cua Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation J. Exp. Med., December 15, 2003; 198(12): 1951 - 1957. [Abstract] [Full Text] [PDF]
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S. Nakae, A. Nambu, K. Sudo, and Y. Iwakura Suppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice J. Immunol., December 1, 2003; 171(11): 6173 - 6177. [Abstract] [Full Text] [PDF]
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W. H. Faour, A. Mancini, Q. W. He, and J. A. Di Battista T-cell-derived Interleukin-17 Regulates the Level and Stability of Cyclooxygenase-2 (COX-2) mRNA through Restricted Activation of the p38 Mitogen-activated Protein Kinase Cascade: ROLE OF DISTAL SEQUENCES IN THE 3'-UNTRANSLATED REGION OF COX-2 mRNA J. Biol. Chem., July 11, 2003; 278(29): 26897 - 26907. [Abstract] [Full Text] [PDF]
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 M. A. Burchill, D. T. Nardelli, D. M. England, D. J. DeCoster, J. A. Christopherson, S. M. Callister, and R. F. Schell Inhibition of Interleukin-17 Prevents the Development of Arthritis in Vaccinated Mice Challenged with Borrelia burgdorferi Infect. Immun., June 1, 2003; 71(6): 3437 - 3442. [Abstract] [Full Text] [PDF]
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Y. Chen, P. Thai, Y.-H. Zhao, Y.-S. Ho, M. M. DeSouza, and R. Wu Stimulation of Airway Mucin Gene Expression by Interleukin (IL)-17 through IL-6 Paracrine/Autocrine Loop J. Biol. Chem., May 2, 2003; 278(19): 17036 - 17043. [Abstract] [Full Text] [PDF]
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 M. Numasaki, J.-i. Fukushi, M. Ono, S. K. Narula, P. J. Zavodny, T. Kudo, P. D. Robbins, H. Tahara, and M. T. Lotze Interleukin-17 promotes angiogenesis and tumor growth Blood, April 1, 2003; 101(7): 2620 - 2627. [Abstract] [Full Text] [PDF]
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R L van Bezooijen, L van der Wee-Pals, S E Papapoulos, and C W G M Lowik Interleukin 17 synergises with tumour necrosis factor {alpha} to induce cartilage destruction in vitro Ann Rheum Dis, October 1, 2002; 61(10): 870 - 876. [Abstract] [Full Text] [PDF]
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M. R. Kim, R. Manoukian, R. Yeh, S. M. Silbiger, D. M. Danilenko, S. Scully, J. Sun, M. L. DeRose, M. Stolina, D. Chang, et al. Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production Blood, September 18, 2002; 100(7): 2330 - 2340. [Abstract] [Full Text] [PDF]
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M. Kurowska, W. Rudnicka, E. Kontny, I. Janicka, M. Chorazy, J. Kowalczewski, M. Ziolkowska, S. Ferrari-Lacraz, T. B. Strom, and W. Maslinski Fibroblast-Like Synoviocytes from Rheumatoid Arthritis Patients Express Functional IL-15 Receptor Complex: Endogenous IL-15 in Autocrine Fashion Enhances Cell Proliferation and Expression of Bcl-xL and Bcl-2 J. Immunol., August 15, 2002; 169(4): 1760 - 1767. [Abstract] [Full Text] [PDF]
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P J Koshy, N Henderson, C Logan, P F Life, T E Cawston, and A D Rowan Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines Ann Rheum Dis, August 1, 2002; 61(8): 704 - 713. [Abstract] [Full Text] [PDF]
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F. Benchetrit, A. Ciree, V. Vives, G. Warnier, A. Gey, C. Sautes-Fridman, F. Fossiez, N. Haicheur, W. H. Fridman, and E. Tartour Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism Blood, March 15, 2002; 99(6): 2114 - 2121. [Abstract] [Full Text] [PDF]
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A. Yamashita, Y. Yonemitsu, S. Okano, K. Nakagawa, Y. Nakashima, T. Irisa, Y. Iwamoto, Y. Nagai, M. Hasegawa, and K. Sueishi Fibroblast Growth Factor-2 Determines Severity of Joint Disease in Adjuvant-Induced Arthritis in Rats J. Immunol., January 1, 2002; 168(1): 450 - 457. [Abstract] [Full Text] [PDF]
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M. Kawaguchi, L. F. Onuchic, X.-D. Li, D. M. Essayan, J. Schroeder, H.-Q. Xiao, M. C. Liu, G. Krishnaswamy, G. Germino, and S.-K. Huang Identification of a Novel Cytokine, ML-1, and Its Expression in Subjects with Asthma J. Immunol., October 15, 2001; 167(8): 4430 - 4435. [Abstract] [Full Text] [PDF]
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E. Lubberts, L. A. B. Joosten, B. Oppers, L. van den Bersselaar, C. J. J. Coenen-de Roo, J. K. Kolls, P. Schwarzenberger, F. A. J. van de Loo, and W. B. van den Berg IL-1-Independent Role of IL-17 in Synovial Inflammation and Joint Destruction During Collagen-Induced Arthritis J. Immunol., July 15, 2001; 167(2): 1004 - 1013. [Abstract] [Full Text] [PDF]
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M. C. Honorati, R. Meliconi, L. Pulsatelli, S. Cane, L. Frizziero, and A. Facchini High in vivo expression of interleukin-17 receptor in synovial endothelial cells and chondrocytes from arthritis patients Rheumatology, May 1, 2001; 40(5): 522 - 527. [Abstract] [Full Text] [PDF]
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E. Chklovskaia, C. Nissen, L. Landmann, C. Rahner, O. Pfister, and A. Wodnar-Filipowicz Cell-surface trafficking and release of flt3 ligand from T lymphocytes is induced by common cytokine receptor {gamma}-chain signaling and inhibited by cyclosporin A Blood, February 15, 2001; 97(4): 1027 - 1034. [Abstract] [Full Text] [PDF]
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T. A. Fehniger and M. A. Caligiuri Interleukin 15: biology and relevance to human disease Blood, January 1, 2001; 97(1): 14 - 32. [Full Text] [PDF]
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F. Luzza, T. Parrello, G. Monteleone, L. Sebkova, M. Romano, R. Zarrilli, M. Imeneo, and F. Pallone Up-Regulation of IL-17 Is Associated with Bioactive IL-8 Expression in Helicobacter pylori-Infected Human Gastric Mucosa J. Immunol., November 1, 2000; 165(9): 5332 - 5337. [Abstract] [Full Text] [PDF]
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